Purpose:
Calculate and plot mutational signatures for all samples using COSMIC signatures and Alexandrov et al, 2013 mutational signatures.
To run this from the command line, use:
Rscript -e "rmarkdown::render('analyses/mutational-signatures/01-known_signatures.Rmd', clean = TRUE)"
This assumes you are in the top directory of the repository.
Import necessary functions.
# Magrittr pipe
`%>%` <- dplyr::`%>%`
# Import specialized functions
source(file.path("util", "mut_sig_functions.R"))
# Load this library
library(deconstructSigs)
library(tidyverse)
── Attaching core tidyverse packages ────────────────────────────────────────────── tidyverse 2.0.0 ──
✔ dplyr 1.1.1 ✔ readr 2.1.4
✔ forcats 1.0.0 ✔ stringr 1.5.0
✔ ggplot2 3.4.2 ✔ tibble 3.2.1
✔ lubridate 1.9.2 ✔ tidyr 1.3.0
✔ purrr 1.0.1
── Conflicts ──────────────────────────────────────────────────────────────── tidyverse_conflicts() ──
✖ dplyr::filter() masks stats::filter()
✖ dplyr::lag() masks stats::lag()
ℹ Use the conflicted package (<http://conflicted.r-lib.org/>) to force all conflicts to become errors
library("optparse")
snv_file <- params$snv_file
output_Folder <- params$output_Folder
Set up directory paths.
data_dir <- file.path("..", "..", "data")
input_dir <- "input"
results_dir <- file.path("results", output_Folder)
plots_dir <- file.path("plots", output_Folder)
figures_dir <- file.path("..", "..", "figures")
cosmicv2_plots <- file.path(plots_dir, "cosmicv2")
nature_plots <- file.path(plots_dir, "nature")
cosmicv3_plots <- file.path(plots_dir, "cosmicv3")
scratch_dir <- file.path("..", "..", "scratch", "mutational-signatures")
cosmicv2_scratch <- file.path(scratch_dir, output_Folder, "cosmicv2")
cosmicv3_scratch <- file.path(scratch_dir, output_Folder, "cosmicv3")
nature_scratch <- file.path(scratch_dir, output_Folder, "nature")
Make new directories for the results.
if (!dir.exists(results_dir)) {
dir.create(results_dir)
}
if (!dir.exists(cosmicv2_plots)) {
dir.create(cosmicv2_plots, recursive = TRUE)
}
if (!dir.exists(nature_plots)) {
dir.create(nature_plots, recursive = TRUE)
}
if (!dir.exists(cosmicv3_plots)) {
dir.create(cosmicv3_plots, recursive = TRUE)
}
if (!dir.exists(scratch_dir)) {
dir.create(scratch_dir)
}
if (!dir.exists(cosmicv2_scratch)) {
dir.create(cosmicv2_scratch)
}
if (!dir.exists(cosmicv3_scratch)) {
dir.create(cosmicv3_scratch)
}
if (!dir.exists(nature_scratch)) {
dir.create(nature_scratch)
}
# Declare file path for consensus file
consensus_file <- file.path(data_dir, snv_file)
Read in the consensus MAF file.
# Read in the file
maf <- data.table::fread(consensus_file, data.table = FALSE)
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in writeBin(bfr, con = out, size = 1L): problem writing to connection
Warning in data.table::fread(consensus_file, data.table = FALSE): Discarded
single-line footer: <<PURPL 0 . GR>>
Read in the histology colors and labels.
histology_label_mapping <- readr::read_tsv(
file.path(figures_dir, "palettes", "histology_label_color_table.tsv")
) %>%
# Select just the columns we will need for plotting
dplyr::select(Kids_First_Biospecimen_ID, display_group, display_order, hex_codes) %>%
# Reorder display_group based on display_order
dplyr::mutate(display_group = forcats::fct_reorder(display_group, display_order))
Rows: 2840 Columns: 15
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (11): Kids_First_Biospecimen_ID, sample_type, integrated_diagnosis, Note...
dbl (4): n, display_order, cancer_group_n, cancer_group_order
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
Set up gradient color palette for the bubble matrix plots.
gradient_col_palette <- readr::read_tsv(
file.path(figures_dir, "palettes", "gradient_color_palette.tsv")
)
Rows: 11 Columns: 2
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (2): color_names, hex_codes
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
# Won't need NA color this time.
gradient_col_palette <- gradient_col_palette %>%
dplyr::filter(color_names != "na_color")
Read in the metadata and set it up with the color palette. Separate BS_ids into intial CNS tumors and other tumors, as mutational signatures analyses will be run on a different set of signatures for each group.
metadata_df <- readr::read_tsv(file.path(data_dir, "histologies.tsv"), guess_max = 10000) %>%
# dplyr::select("Kids_First_Biospecimen_ID", "experimental_strategy") %>%
dplyr::inner_join(histology_label_mapping, by = "Kids_First_Biospecimen_ID") %>%
dplyr::rename(Tumor_Sample_Barcode = "Kids_First_Biospecimen_ID")
Rows: 47507 Columns: 58
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (41): Kids_First_Participant_ID, Kids_First_Biospecimen_ID, sample_id, a...
dbl (17): cell_line_passage, OS_days, EFS_days, age_at_diagnosis_days, age_a...
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
initial_pretx_tumors <- metadata_df %>%
filter(tumor_descriptor == "Initial CNS Tumor" & age_at_diagnosis_days < age_at_chemo_start) %>%
pull(Tumor_Sample_Barcode)
Read in tmb-all file with WGS and WXS region lengths so they can be used for the Mb denominator.
# Set up BED region file for TMB calculations
region_sizes <- readr::read_tsv(file.path(data_dir, "snv-mutation-tmb-all.tsv")) %>%
dplyr::select(Tumor_Sample_Barcode, region_size)
Rows: 4148 Columns: 5
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (2): Tumor_Sample_Barcode, experimental_strategy
dbl (3): mutation_count, region_size, tmb
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
Determine how many mutations we have per sample.
mut_per_sample <- maf %>%
dplyr::group_by(Tumor_Sample_Barcode) %>%
dplyr::tally() %>%
dplyr::arrange(n)
summary(mut_per_sample$n)
Min. 1st Qu. Median Mean 3rd Qu. Max.
8.0 146.8 1625.5 2912.3 2881.8 171779.0
Graph this.
ggplot2::ggplot(mut_per_sample, ggplot2::aes(x = n, geom = "density")) +
ggplot2::geom_density() +
ggplot2::theme_classic()
Make mutation data into deconstructSigs input
format.
# Convert to deconstructSigs input
sigs_input <- mut.to.sigs.input(
mut.ref = maf,
sample.id = "Tumor_Sample_Barcode",
chr = "Chromosome",
pos = "Start_Position",
ref = "Reference_Allele",
alt = "Allele",
bsg = BSgenome.Hsapiens.UCSC.hg38::BSgenome.Hsapiens.UCSC.hg38
)
Warning in mut.to.sigs.input(mut.ref = maf, sample.id = "Tumor_Sample_Barcode", : Some samples have fewer than 50 mutations:
BS_7KR13R3P, BS_Z8GRJ71M, BS_YGDHJ68W, BS_X0KN4VVW, BS_W60PB1DS, BS_ST7KGV85, BS_QF7M4SHH, BS_P7VR731D, BS_KT3GAAQV, BS_KHJMCFQR, BS_GQFPB8F3, BS_GJ2KS7BT, BS_BTDQZ60Q, BS_91HP99HY, BS_4SCDT7M9, BS_3DV5FVPQ, BS_1B00Q25Y, BS_02QV7ZWP
Add total mutations per sample.
# Count the total number of signature mutations for each sample
total_muts <- apply(sigs_input, 1, sum)
Get list of tumor sample ids.
tumor_sample_ids <- maf %>%
dplyr::filter(Tumor_Sample_Barcode %in% rownames(sigs_input)) %>%
dplyr::distinct(Tumor_Sample_Barcode) %>%
dplyr::pull(Tumor_Sample_Barcode)
Get COSMIC v2 signatures for each sample. This step will take some time.
sample_sigs_cosmic <- lapply(tumor_sample_ids, function(sample_id) {
# Determine the signatures contributing to the sample
whichSignatures(
tumor.ref = sigs_input,
signatures.ref = signatures.cosmic,
sample.id = sample_id,
contexts.needed = TRUE
)
})
# Bring along the names
names(sample_sigs_cosmic) <- tumor_sample_ids
# Create matrix of COSMIC signature weights
cosmic_weights <- lapply(sample_sigs_cosmic, "[[", "weights")
cosmic_wide <- do.call(dplyr::bind_rows, cosmic_weights) %>%
add_column('Kids_First_Biospecimen_ID' = unlist(lapply(cosmic_weights, rownames)), .before = 1) %>%
tibble::as_tibble() %>%
readr::write_tsv(file.path(results_dir, 'cosmicv2_signature_exposure_matrix.tsv'))
Get Alexandrov et al, 2013 signatures for each sample.
sample_sigs_nature <- lapply(tumor_sample_ids, function(sample_id) {
# Determine the signatures contributing to the sample
whichSignatures(
tumor.ref = sigs_input,
signatures.ref = signatures.nature2013,
sample.id = sample_id,
contexts.needed = TRUE
)
})
# Bring along the names
names(sample_sigs_nature) <- tumor_sample_ids
# Create data frame of Nature signature weights
nature_weights <- lapply(sample_sigs_nature, "[[", "weights")
nature_wide <- do.call(dplyr::bind_rows, nature_weights) %>%
add_column('Kids_First_Biospecimen_ID' = unlist(lapply(nature_weights, rownames)), .before = 1) %>%
tibble::as_tibble() %>%
readr::write_tsv(file.path(results_dir, 'nature_signature_exposure_matrix.tsv'))
Get COSMIC genome v3.3 signatures for each sample.
signatures.cosmic.v3.3 <- read_tsv(file.path(input_dir, 'COSMIC_v3.3.1_SBS_GRCh38.txt')) %>%
column_to_rownames('Type') %>%
t %>%
as.data.frame()
Rows: 96 Columns: 80
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (1): Type
dbl (79): SBS1, SBS2, SBS3, SBS4, SBS5, SBS6, SBS7a, SBS7b, SBS7c, SBS7d, SB...
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
Create list of include/exclude signatures using SBSv3 mapping file. For Initial CNS tumors, therapy exposures will be excluded, but they will be retained for other tumor types.
map <- read_tsv(file.path(input_dir, "sbs_v3_map.tsv"))
Rows: 79 Columns: 4
── Column specification ──────────────────────────────────────────────────────────────────────────────
Delimiter: "\t"
chr (4): Signature, Meaning, Broad_category, Narrow_category
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.
# Excluded signatures:
artifact_sigs <- map %>%
filter(Broad_category == "Sequencing artifact") %>%
pull(Signature)
environ_sigs <- map %>%
filter(Broad_category == "Environmental exposure") %>%
pull(Signature)
unknown <- map %>%
filter(Broad_category == "Unknown" & Signature != "SBS39") %>%
pull(Signature)
therapy_sigs <- map %>%
filter(Broad_category == "Therapy exposure") %>%
pull(Signature)
exclude_sigs <- c(artifact_sigs, environ_sigs, unknown)
include_sigs_initialPretx <- setdiff(rownames(signatures.cosmic.v3.3), c(exclude_sigs, therapy_sigs))
include_sigs_other <- setdiff(rownames(signatures.cosmic.v3.3), exclude_sigs)
Run signature extraction. This step will take some time.
sample_sigs_cosmic_v33 <- lapply(tumor_sample_ids, function(sample_id) {
# Determine the signatures contributing to the sample
if (sample_id %in% initial_pretx_tumors){
whichSignatures(
tumor.ref = sigs_input,
signatures.ref = signatures.cosmic.v3.3,
sample.id = sample_id,
contexts.needed = TRUE,
associated = include_sigs_initialPretx
)
}else{
whichSignatures(
tumor.ref = sigs_input,
signatures.ref = signatures.cosmic.v3.3,
sample.id = sample_id,
contexts.needed = TRUE,
associated = include_sigs_other
)
}
})
# Bring along the names
names(sample_sigs_cosmic_v33) <- tumor_sample_ids
#
# Create matrix of COSMIC signature weights
cosmic_v33_weights <- lapply(sample_sigs_cosmic_v33, "[[", "weights")
cosmic_v33_wide <- do.call(dplyr::bind_rows, cosmic_v33_weights) %>%
add_column('Kids_First_Biospecimen_ID' = unlist(lapply(cosmic_v33_weights, rownames)), .before = 1) %>%
tibble::as_tibble() %>%
readr::write_tsv(file.path(results_dir, 'cosmicv3.3_signature_exposure_matrix.tsv'))
Do this for COSMIC v2 mutation signatures.
# Calculate mutations per signature
cosmic_sigs_df <- calc_mut_per_sig(
sample_sigs_cosmic,
muts_per_sample = total_muts,
region_size = region_sizes,
metadata = metadata_df
) %>%
dplyr::filter(grepl("Signature", signature))
Using Tumor_Sample_Barcode, Kids_First_Participant_ID, sample_id, aliquot_id, sample_type, tumor_descriptor, composition, cell_line_composition, pathology_diagnosis, pathology_free_text_diagnosis, cancer_predispositions, cohort, sub_cohort, experimental_strategy, RNA_library, match_id, cohort_participant_id, primary_site, CNS_region, reported_gender, germline_sex_estimate, race, ethnicity, OS_status, EFS_event_type, extent_of_tumor_resection, clinical_status_at_event, seq_center, broad_histology, short_histology, molecular_subtype, molecular_subtype_methyl, cancer_group, integrated_diagnosis, harmonized_diagnosis, Notes, dkfz_v12_methylation_subclass, dkfz_v12_methylation_mgmt_status, dkfz_v11_methylation_subclass, gtex_group, gtex_subgroup, display_group, hex_codes as id variables
Warning: attributes are not identical across measure variables; they will be
dropped
# Write this to a file but drop the color column
cosmic_sigs_df %>%
dplyr::select(-hex_codes) %>%
readr::write_tsv(file.path(results_dir, "cosmicv2_signatures_results.tsv"))
# Print out a preview
cosmic_sigs_df
Do this for COSMIC v3.3 mutation signatures.
# Calculate mutations per signature
cosmicv3_sigs_df <- calc_mut_per_sig(
sample_sigs_cosmic_v33,
muts_per_sample = total_muts,
region_size = region_sizes,
metadata = metadata_df
) %>%
dplyr::filter(grepl("SBS", signature))
Using Tumor_Sample_Barcode, Kids_First_Participant_ID, sample_id, aliquot_id, sample_type, tumor_descriptor, composition, cell_line_composition, pathology_diagnosis, pathology_free_text_diagnosis, cancer_predispositions, cohort, sub_cohort, experimental_strategy, RNA_library, match_id, cohort_participant_id, primary_site, CNS_region, reported_gender, germline_sex_estimate, race, ethnicity, OS_status, EFS_event_type, extent_of_tumor_resection, clinical_status_at_event, seq_center, broad_histology, short_histology, molecular_subtype, molecular_subtype_methyl, cancer_group, integrated_diagnosis, harmonized_diagnosis, Notes, dkfz_v12_methylation_subclass, dkfz_v12_methylation_mgmt_status, dkfz_v11_methylation_subclass, gtex_group, gtex_subgroup, display_group, hex_codes as id variables
Warning: attributes are not identical across measure variables; they will be
dropped
# Write this to a file but drop the color column
cosmicv3_sigs_df %>%
# dplyr::filter(grepl("SBS", signature)) %>%
dplyr::select(-hex_codes) %>%
readr::write_tsv(file.path(results_dir, "cosmicv3.3_signatures_results.tsv"))
# Print out a preview
cosmicv3_sigs_df
Do this for Alexandrov et al, 2013 mutation signatures.
#Calculate mutations per signature
nature_sigs_df <- calc_mut_per_sig(
sample_sigs_nature,
muts_per_sample = total_muts,
region_size = region_sizes,
metadata = metadata_df
) %>%
dplyr::filter(grepl("Signature", signature))
Using Tumor_Sample_Barcode, Kids_First_Participant_ID, sample_id, aliquot_id, sample_type, tumor_descriptor, composition, cell_line_composition, pathology_diagnosis, pathology_free_text_diagnosis, cancer_predispositions, cohort, sub_cohort, experimental_strategy, RNA_library, match_id, cohort_participant_id, primary_site, CNS_region, reported_gender, germline_sex_estimate, race, ethnicity, OS_status, EFS_event_type, extent_of_tumor_resection, clinical_status_at_event, seq_center, broad_histology, short_histology, molecular_subtype, molecular_subtype_methyl, cancer_group, integrated_diagnosis, harmonized_diagnosis, Notes, dkfz_v12_methylation_subclass, dkfz_v12_methylation_mgmt_status, dkfz_v11_methylation_subclass, gtex_group, gtex_subgroup, display_group, hex_codes as id variables
Warning: attributes are not identical across measure variables; they will be
dropped
# Write this to a file but drop the color column
nature_sigs_df %>%
# dplyr::filter(grepl("SBS", signature)) %>%
dplyr::select(-hex_codes) %>%
readr::write_tsv(file.path(results_dir, "nature_signatures_results.tsv"))
# Print out a preview
nature_sigs_df
For COSMIC v2 signatures
bubble_matrix_plot(cosmic_sigs_df,
label = "COSMIC Signatures",
color_palette = gradient_col_palette$hex_codes
)
`summarise()` has grouped output by 'display_group'. You can override using the
`.groups` argument.
Warning: Removed 335 rows containing missing values (`geom_point()`).
ggplot2::ggsave(
file.path(cosmicv2_plots, "bubble_matrix_cosmicv2_mutation_sig.png"),
width = 30, height = 20, units = "cm")
Warning: Removed 335 rows containing missing values (`geom_point()`).
For Nature signatures
bubble_matrix_plot(nature_sigs_df,
label = "Alexandrov et al, 2013 signatures",
color_palette = gradient_col_palette$hex_codes)
`summarise()` has grouped output by 'display_group'. You can override using the
`.groups` argument.
Warning: Removed 281 rows containing missing values (`geom_point()`).
ggplot2::ggsave(
file.path(nature_plots, "bubble_matrix_nature_mutation_sig.png"),
width = 30, height = 20, units = "cm")
Warning: Removed 281 rows containing missing values (`geom_point()`).
For COSMIC v3.3 signatures
bubble_matrix_plot(cosmicv3_sigs_df,
label = "COSMIC Signatures",
color_palette = gradient_col_palette$hex_codes
)
`summarise()` has grouped output by 'display_group'. You can override using the
`.groups` argument.
Warning: Removed 1116 rows containing missing values (`geom_point()`).
ggplot2::ggsave(
file.path(cosmicv3_plots, "bubble_matrix_cosmicv3_mutation_sig.png"),
width = 30, height = 20, units = "cm")
Warning: Removed 1116 rows containing missing values (`geom_point()`).
We will make these plots for primary tumor samples only. Lets make these for COSMIC mutation signatures first.
# Make grouped bar plots
lapply(unique(cosmic_sigs_df$display_group),
grouped_sig_barplot,
sig_num_df = cosmic_sigs_df,
output_dir = file.path(cosmicv2_scratch, "signature_grouped_barplots"),
label = "cosmic_v2"
)
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Make these plots for Alexandrov et al, 2013 signatures.
# Make grouped bar plots
lapply(unique(nature_sigs_df$display_group),
grouped_sig_barplot,
sig_num_df = nature_sigs_df,
output_dir = file.path(nature_scratch, "signature_grouped_barplots"),
label = "nature"
)
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Make these plots for COSMIC v3.3 signatures.
# Make grouped bar plots
lapply(unique(cosmicv3_sigs_df$display_group),
grouped_sig_barplot,
sig_num_df = cosmicv3_sigs_df,
output_dir = file.path(cosmicv3_scratch, "signature_grouped_barplots"),
label = "cosmic_v3.3"
)
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
Saving 7 x 5 in image
sessionInfo()
R version 4.2.3 (2023-03-15)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Ubuntu 22.04.2 LTS
Matrix products: default
BLAS: /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3
LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.20.so
locale:
[1] LC_CTYPE=en_US.UTF-8 LC_NUMERIC=C
[3] LC_TIME=en_US.UTF-8 LC_COLLATE=en_US.UTF-8
[5] LC_MONETARY=en_US.UTF-8 LC_MESSAGES=en_US.UTF-8
[7] LC_PAPER=en_US.UTF-8 LC_NAME=C
[9] LC_ADDRESS=C LC_TELEPHONE=C
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C
attached base packages:
[1] stats graphics grDevices utils datasets methods base
other attached packages:
[1] optparse_1.7.3 lubridate_1.9.2 forcats_1.0.0
[4] stringr_1.5.0 dplyr_1.1.1 purrr_1.0.1
[7] readr_2.1.4 tidyr_1.3.0 tibble_3.2.1
[10] ggplot2_3.4.2 tidyverse_2.0.0 deconstructSigs_1.9.0
loaded via a namespace (and not attached):
[1] Biobase_2.58.0 MatrixGenerics_1.10.0
[3] sass_0.4.5 bit64_4.0.5
[5] vroom_1.6.1 jsonlite_1.8.4
[7] R.utils_2.12.2 bslib_0.4.2
[9] highr_0.10 stats4_4.2.3
[11] BSgenome_1.66.3 GenomeInfoDbData_1.2.9
[13] Rsamtools_2.14.0 yaml_2.3.7
[15] lattice_0.21-8 pillar_1.9.0
[17] glue_1.6.2 digest_0.6.31
[19] GenomicRanges_1.50.2 XVector_0.38.0
[21] colorspace_2.1-0 plyr_1.8.8
[23] Matrix_1.5-4 htmltools_0.5.5
[25] R.oo_1.25.0 XML_3.99-0.14
[27] pkgconfig_2.0.3 zlibbioc_1.44.0
[29] scales_1.2.1 getopt_1.20.3
[31] tzdb_0.3.0 BiocParallel_1.32.6
[33] timechange_0.2.0 generics_0.1.3
[35] farver_2.1.1 IRanges_2.32.0
[37] SummarizedExperiment_1.28.0 cachem_1.0.7
[39] withr_2.5.0 BiocGenerics_0.44.0
[41] cli_3.6.1 magrittr_2.0.3
[43] crayon_1.5.2 evaluate_0.20
[45] R.methodsS3_1.8.2 fansi_1.0.4
[47] textshaping_0.3.6 tools_4.2.3
[49] data.table_1.14.8 hms_1.1.3
[51] BiocIO_1.8.0 lifecycle_1.0.3
[53] matrixStats_0.63.0 S4Vectors_0.36.2
[55] munsell_0.5.0 DelayedArray_0.24.0
[57] Biostrings_2.66.0 compiler_4.2.3
[59] jquerylib_0.1.4 GenomeInfoDb_1.34.9
[61] systemfonts_1.0.4 rlang_1.1.0
[63] grid_4.2.3 RCurl_1.98-1.12
[65] rjson_0.2.21 bitops_1.0-7
[67] labeling_0.4.2 rmarkdown_2.21
[69] restfulr_0.0.15 gtable_0.3.3
[71] codetools_0.2-19 reshape2_1.4.4
[73] R6_2.5.1 GenomicAlignments_1.34.1
[75] knitr_1.42 rtracklayer_1.58.0
[77] fastmap_1.1.1 bit_4.0.5
[79] utf8_1.2.3 ragg_1.2.5
[81] stringi_1.7.12 Rcpp_1.0.10
[83] parallel_4.2.3 vctrs_0.6.2
[85] tidyselect_1.2.0 xfun_0.38
[87] BSgenome.Hsapiens.UCSC.hg38_1.4.5